HER2-CAR T Cells in Treating Patients With Recurrent Brain or Leptomeningeal Metastases

Running, not enrolling · Phase 1

Conditions studied: Malignant Neoplasm, Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Neoplasm in the Leptomeninges, Breast Cancer, HER2-positive Breast Cancer

In brief

This phase I trial studies the side effects and best dose of HER2-CAR T cells in treating patients with cancer that has spread to the brain or leptomeninges and has come back (recurrent). HER2-CAR T cells delivered into the ventricles of the brain may recognize and kill tumor cells.

Key facts

Study ID

NCT03696030

Run by

City of Hope Medical Center

People needed

24

Starts

2018-08-31

Expected to finish

2027-01-24

Last updated by the study team

2026-04-23

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• SCREENING: Participant has treated brain and/or leptomeningeal metastases that has not recurred OR
• Such participants are eligible to enroll in the study and undergo leukapheresis, but they cannot start treatment with HER2-CAR T cells until there is evidence of tumor progression/recurrence
• SCREENING: Participant has recurrent brain metastases after radiation therapy OR
• SCREENING: Participant has recurrent leptomeningeal metastases after intrathecal chemotherapy OR
• SCREENING: Participant has untreated brain or leptomeningeal metastases and refuses to undergo radiation and/or intrathecal chemotherapy
• Note: Participants with leptomeningeal metastasis (diagnosed by positive CSF cytology or characteristic findings on brain or spine magnetic resonance imaging [MRI]) may have concomitant brain metastases, but having both is not required
• SCREENING: Participant must have a Karnofsky performance status (KPS) >= 70
• SCREENING: Participant must have a life expectancy of >= 8 weeks
• SCREENING: The effects of HER2-CAR T cells on a developing fetus are unknown. For this reason, women of child-bearing potential must have negative serum pregnancy test and agree to use a reliable form of birth control prior to study entry and for at least two months following duration of study participation. Male research participants must agree to use a reliable form of birth control and not donate sperm during the study and for at least six months afterwards
• SCREENING: Participant has a histologically confirmed cancer which is HER2+, defined as 3+ by immunohistochemistry (IHC) or gene amplification by fluorescence in situ hybridization (FISH)
• SCREENING: Participant must have the ability to understand and the willingness to sign a written informed consent
• ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: At least 2 weeks must have elapsed since the participant received his/her last dose of prior targeted agents, chemotherapy or radiation; at the PI's discretion, exception can be made for investigational agents that are delivered locally into the CSF
• ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: Research participant must not require more than 6 mg/day of dexamethasone (or the equivalent dose of another corticosteroid) on the day of leukapheresis
• ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: Participant must be willing to undergo placement of a catheter for central venous access if s/he does not have adequate peripheral venous access for collection of T cells
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Creatinine < 1.6 mg/dL
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: White blood cell (WBC) > 2,000/uL (or absolute neutrophil count [ANC] > 1,000)
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Platelets >= 100,000/uL
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: International normalized ratio (INR) must be < 1.3
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Bilirubin < 1.5 mg/dL
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X upper limits of normal
• ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF HER2-CAR T CELLS: Participant must be taking =< 6 mg/ day of dexamethasone (or the equivalent dose of another corticosteroid) during CAR T cell therapy
• ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF HER2-CAR T CELLS: Participants agrees to stop treatment with chemotherapy or endocrine therapy during the first 3 cycles of the HER2-CAR T cell study
• ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF HER2-CAR T CELLS: Participant does not have evidence of active infection and does not have a fever exceeding 38.5 degrees C; there is an absence of positive blood culture for bacteria, fungus, or virus within 48-hours prior to HER2-CAR T cell infusion and/or there aren't any indications of meningitis
• ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF HER2-CAR T CELLS: WBC > 2,000/uL (or ANC > 1,000)
• ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF HER2-CAR T CELLS: Platelets > 100,000/uL. However, if platelet level is between 75,000-99,000/uL then HER2-CAR T-cell administration may proceed after platelet transfusion is given, and the post transfusion platelet count is >= 100,000/uL

You may not qualify if…

• EXCLUSION CRITERIA FOR STUDY SCREENING: Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
• EXCLUSION CRITERIA FOR STUDY SCREENING: Research participants with a known history of congestive heart failure (CHF) or cardiac symptoms consistent with NYHA classification III-IV within 6 months prior to day 1 of protocol treatment, cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications or with clinical history suggestive of the above must have an EKG and echocardiogram (ECHO) performed within 42 days prior to registration and as clinically indicated while on treatment.
• Research participants with new symptoms of CHF, cardiomyopathy, myocarditis, MI, or exposure to cardiotoxic medications must have a cardiac consultation, creatinine phosphokinase (CPK), and troponin testing at pre study and as clinically indicated
• EXCLUSION CRITERIA FOR STUDY SCREENING: Research participant requires dialysis
• EXCLUSION CRITERIA FOR STUDY SCREENING: Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• EXCLUSION CRITERIA FOR STUDY SCREENING: Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase 1 study. A legal guardian may substitute for the research participant
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is unwilling to stop treatment with chemotherapy or endocrine therapy during the first 3 cycles of the HER2-CAR T cell study
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has a coagulopathy or bleeding disorder or cannot safely discontinue anticoagulation prior to placement of a Rickham reservoir
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has a chronic or active viral infection of the CNS
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has any uncontrolled illness, including ongoing or active infection; participant has known active hepatitis B or C infection; participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of screening
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has an autoimmune disease
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has another active malignancy
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participants with lung metastases (exception may be allowed per principal investigator [PI] discretion for participants that are not symptomatic from their lung metastases)
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is unable to undergo a brain MRI
• EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is breast feeding. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HER2-CAR T cells, breastfeeding should be discontinued if the mother wants to participate in this study
• EXCLUSION CRITERIA FOR STUDY SCREENING: Patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol

Where it is running

• City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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